tbuckley/cabot-search huggingface dataset:
Abstract LB200: Pdgf/Pi3k/akt axis activation by hey1-ncoa2 fusion and potential target in the treatment of mesenchymal chondrosarcoma
Authors: Wenqing Qi, Lu Wang
Journal: Cancer Research (2022)

Abstract Mesenchymal chondrosarcoma is a rare and often aggressive cancer mostly affecting children and young adults. Genetically, this tumor is mainly characterized by the recurrent HEY1-NCOA2 fusion. Localized tumor is managed surgically; traditional chemotherapy and radiation therapy, however, did not appear to substantially improve the event-free survival rate of mesenchymal chondrosarcoma patients. It is clear that better therapeutic options are needed for the treatment of this tumor. In our previous study, an in vitro model for studying mesenchymal chondrosarcoma tumorigenesis was developed using stably transduced iPSC-derived mesenchymal stem cells (iPSC-MSCs) with inducible-expression of HEY1-NCOA2. With the in vitro model, we performed genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) and RNA-seq to identify HEY1-NCOA2-dependent transcriptional regulation and demonstrated the dramatic activation of PDGF-PDGFR and PI3K-AKT signaling pathways (manuscript in review). Our data also suggested that PDGFB is one of the direct targets of HEY1-NCOA2 fusion protein. In the present study, with the in vitro iPSC-MSC model, we verified that HEY1-NCOA2 fusion protein, but not wild-type HEY1 or NCOA2, dramatically increased phospho-AKT (Ser473, a readout of PI3K) expression by western blotting. Further on, we tested the effect of two kinase inhibitors CP-673451 and PF-04691502, a potent and selective PDGFR inhibitor and the mTOR/PI3K inhibitor, respectively. Stably transfused iPSC-MSC were treated with the kinase inhibitors, respectively, at different dosages (0.1 µM, 0.5 µM and 1.0 µM) for one week. At the concentration of 1.0 µM, CP-673451 efficiently suppressed AKT phosphorylation by ~23% as well as suppressed cell growth by ~67% which is significantly higher than that observed in the controls (e.g. ~20% suppression in HEY1- and NCOA2- expression iPSC-MSCs). Similarly, at the concentration of 0.5 µM, PF-04691502 suppressed the HEY1-NCOA2-expression iPSC-MSCs growth by ~24% more than that in the control (p=0.02). In summary, both CP-673451 and PF-04691502 were active against the in vitro mesenchymal chondrosarcoma model tested. Based on these data, the potential benefit of targeting PDGF/PI3K/AKT signaling pathways in the treatment of mesenchymal chondrosarcoma was suggested. Citation Format: Wenqing Qi, Lu Wang. Pdgf/Pi3k/akt axis activation by hey1-ncoa2 fusion and potential target in the treatment of mesenchymal chondrosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB200.
PB2332: PREVALENCE OF HYPERHOMOCYSTEINEMIA IN PATIENTS WITH DEEP VEIN THROMBOSIS
Authors: B. Mariem, S. Fendri, B. S. Raida, J. Kamel, B. Zouheir
Journal: HemaSphere (2022)

Background: Deep vein thrombosis is a public health problem for which the etiological research is an essential step in the management. Numerous studies have shown an association between hyperhomocysteinemia and venous thrombosis. Aims: In the course of our work, we set out to study the relationship between deep vein thrombosis and homocysteine. Methods: This is an observational case-control study comparing 47 patients admitted to the internal medicine department for the management of deep vein thrombosis confirmed by radiological examination, with 47 healthy controls. These two groups were matched in age, sex and body mass index. The homocysteine ​​assay was done by an enzymatic technique. Results: The mean age of patients and controls was 40.8 ± 10.5 years with extremes of 18 and 59 years. The two groups consisted of 27 men (57.5%) and 20 women (42.5%) with a sex ratio of 1.35. Homocysetine was significantly (p <0.001) in patients (17.42 ± 8.5 µmol / L) compared to controls (9.41 ± 3.1 µmol / L), with a prevalence of hyperhomocysteinemia (defined by a homocysteine ​​level> 15 µmol / L) of 61.7% in the patients against 4% in the controls. HHC was found to be significantly correlated with the occurrence of deep vein thrombosis with an odds ratio of 3.54 with a 95% confidence interval [1.76 - 16.4] compared to the control group. Summary/Conclusion: Homocysteine ​​is an intermediate sulfur amino acid in the metabolism of methionine and cysteine, the increase in which has been shown to be associated with the risk of developing deep vein thrombosis.
PB2315: EFFICACY AND SAFETY OF TWO DIFFERENT LOW-DOSE RITUXIMAB REGIMENS FOR CHINESE CHILDREN PATIENTS WITH PRIMARY IMMUNE THROMBOCYTOPENIA
Authors: X. Zhu
Journal: HemaSphere (2022)

Background: Rituximab is one of the second-line treatments for ITP. At present, there are few studies on low-dose rituximab, lacking of a large number of prospective and randomized trials to support the efficacy and safety of low-dose rituximab, especially in children’s ITP. Influenced by COVID-19, we used two low-dose rituximab regimens before and after March 2020 for second-line treatment of children’s ITP. Aims: To compare the efficacy and safety of two different regimens for low-dose rituximab of children patients with chronic /refractory ITP, so as to provide basis for clinical treatment. Methods: 83 children patients were enrolled in this study and non-randomly assigned to receive 100mg/200mg (body weight 30kg) rituximab weekly for 4 weeks (group A, 53 cases) or a single dose of 375mg / m2 rituximab (group B, 30cases). The study was follow-up for at least half a year. Results: The baseline data of group A and B were the same. For group A: Overall and complete response (OR and CR) rates were 35.8% and 15%, respectively; the side effects rate is 3.8%. In responders, the median time to response was 4 (1 -12) weeks, with a median follow-up time of 12 (6 ~ 36) months, 6 of 19 responders (31.6%) relapsed. For group B: OR and CR rates were 36.7% and 23%, respectively; the side effects rate is 10%. In responders, the median time to response was 1 (1 ~ 4) weeks, with a median follow-up time of 11.5 (6 ~ 17) months, 4 of 11 responders (36.4%) relapsed. No significant difference in the OR, NR, relapse free survival and incidence of side effects was observed in patients between the two groups. Image:Summary/Conclusion: The two low-dose rituximab regimens in the treatment of ITP in children both are safe and effective; The single-agent scheme is more recommended because of easier use and not increasing safety events.
P1571: EVALUATION OF THE CLINICAL IMPACT OF BONE MARROW CULTURES IN CURRENT MEDICAL PRACTICE
Authors: G. Sharvit, D. Schwartz, G. Heering, A. Shulman, A. Avigdor, G. Rahav, A. Toren, A. Nagler, J. Canaani
Journal: HemaSphere (2022)

Background: The clinical yield and benefit of performing bone marrow cultures for various clinical indications has been challenged and their clinical necessity remains debatable. Aims: To characterize a large cohort of patients who had bone marrow cultures performed in terms of baseline clinical, laboratory, microbiological, and imaging data, and determine whether these parameters were predictive of a diagnostic bone marrow culture. Methods: A single center retrospective analysis of all patients who underwent a bone marrow study comprising bone marrow cultures from January 1, 2012, through March 1, 2018. Data on comorbidities, baseline laboratory parameters, and indication for performing a bone marrow culture were extracted from the institution’s electronic medical records system. Results: The analyzed cohort consisted of 139 patients admitted to our institution between the years 2012-2018 with a median age of 46 years (range 4 months- 85 years). The most common indication for a bone marrow study was workup of a fever of unknown origin (105 patients, 76%) while investigation for infection in immunocompromised patients accounted for 22 cases (16%) and suspected tuberculosis was the reason for acquisition of bone marrow cultures in 6 patients (4%). Of all patients who underwent bone marrow examinations with culture studies, only 3 patients had positive bone marrow cultures yielding in 2 patients a diagnosis of Mycobacterium avium and in one patient a microbiologically unclassifiable fungal infection. A univariate analysis revealed that mean age, hemoglobin level, platelet count, c-reactive protein levels, gender, indication for bone marrow study, yield of blood cultures, and contribution of imaging studies and bone marrow pathology results were not significantly different between patients with diagnostic bone marrow cultures and those with non-diagnostic bone marrow cultures. Mean white blood cell count was found to be significantly lower in patients with diagnostic bone marrow cultures (2.4 ×103/µL versus 8.7 ×103/µL; P=.038). Summary/Conclusion: For most patients, performance of bone marrow cultures holds limited clinical value.
P1690: NEUTROPHIL EXTRACELLULAR TRAP (NET) LEVELS IN COVID-19 PATIENTS
Authors: L. López De Frutos, I. Serrano-Gonzalo, I. Arevalo-Vargas, B. Menéndez-Jandula, E. Franco-García, C. Lahoz, P. Latre, R. Köhler, P. Giraldo
Journal: HemaSphere (2022)

Background: Innate and adaptative immune responses are triggered by the SARS-CoV-2 infection and induces an exacerbate cytokine storms responsible from a septic shock, acute respiratory distress and/or multiple organs failure. As part of the response against infection, neutrophils release the neutrophil extracellular traps (NETs), as a mechanism to encapsulate the infective agent and reduce it, but an overproduction is related with several inflammatory and thrombotic complications. Aims: As the production of microthrombi and endothelial damage is one of the complications due to SARS-CoV-2 infection we would evaluate several molecules linked to the NETosis process in patients infected during the first wave and compare them with levels in general population (pre-Covid) and patients during January 2021 wave. Methods: Two plasma samples from 60 patients with SARS-CoV-2 infection were provided by the Aragon Health System Biobank (30 for each wave), the first sample just after the diagnosis and the second one seven days later, as well as 100 control samples obtained before May 2019. Demographic data, clinical manifestations, associated comorbidities and thrombotic complications were collected. Myeloperoxidase (MPO), neutrophil elastase (NE), S100A8/S1009A heterodimer (MPR) and P-Selectine (P-SEL) were evaluated by immunoquantification meanwhile circulating free DNA (cfDNA) and DNAses concentration were assessed by fluorometry, always following the manufacturer instructions. Statistical analysis was performed by SPSS software using non-parametric test for independent and related samples. Results: Infected patients have a significantly increase of MRP (p<0.001) and NE (p<0.001) meanwhile P-SEL and DNAsa concentration was significantly decreased (p<0.001). The patients did not show any differences between first and second sample. But, differences between patients from each wave were significant for NE, MPO, and P-SEL (p>0.001), with lower levels of NE and higher MPO and P-SEL in those patients affected in the first wave. Summary/Conclusion: In conclusion, the study demonstrates a NETs activation in infected patients that can be related with the increased risk of thrombotic events and vascular damage in infected patients. The differences between groups of patients are under analysis and can be influenced by age at infection. The correlation with the demographic data, comorbidities and complications is ongoing. This work is ongoing with the support of a research grant from FEETEG.
PB2090: TREATMENT OUTCOME OF ORBITAL MARGINAL ZONE B CELL LYMPHOMA -- TEN YEARS FOLLOW UP IN A SINGLE INSTITUTION
Authors: T.-D. Tan, L.-W. Chiou, H.-C. Kau
Journal: HemaSphere (2022)

Background: Marginal zone B cell lymphoma (MZBCL) is one of indolent B cell lymphoma including nodal, extra-nodal, and splenic types. The extra-nodal MZBCL includes gastric, bronchial, bowel, salivary gland, thyroid, and orbital MALT lymphoma. As the indolent in character, we know that durable survival is expected but relapse could be not unusual. Aims: To analyze the treatment modality and outcome in real world experence. Methods: Between 2009 and 2018, 10 patients of orbital MZBCL and we analyzed the treatment modality and outcome in our institution. Results: Between 2009 and 2018, 10 patients of orbital MZBCL with median age 43 (range 33 to 63) and male/female was 6/4. Seven patients were in stage I (70%), one in stage II (10%), and 2 in stage IV (20%). Five patients underwent radiotherapy alone, two underwent chemo-immunotherapy (R-CVP) followed by radiation, and three of them underwent chemo-immunotherapy without radiation. Three of them got lymphoma relapsed including one had large B cell transformation and second complete remission after salvage chemo-immunotherapy. All ten patients are survived at the time of report. Image:Summary/Conclusion: High overall survival (100%) and progression free survival (70%) in our cohort and two of the relapsed patients were stage IV disease and another patient had large localized tumor.
PB1821: COMBINATION OF BCL-2 INHIBITOR, HYPOMETHYLATION AGENTS AND LOW-DOSE CYTARABINE AS A SALVAGE THERAPY FOR ACUTE MYELOID LEUKEMIA AND MYELODYSPLASTIC SYNDROMES
Authors: X.-N. Gao, X. Lou, J. Lin, Y.-F. Su, J. Wang, L. Xu, H. Yu, A. Wang, Y.-Z. Wang, D.-H. Liu
Journal: HemaSphere (2022)

Background: Although studies are ongoing to evaluate the efficiency and safety of venetoclax-based therapy, alone or in combination with hypomethylation agent or low-dose cytarabine, in relapsed/refractory acute myeloid leukemia, data are scarce and heterogenous. Herein, we report our experience of a new venetoclax-based triple-drug combination regimen in acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) in the salvage setting. Aims: To assess safety and response to venetoclax + hypomethylation agent + low-dose cytarabine regimen after minimum 1 cycle of therapy in patients with AML or MDS, who developed morphologic or molecular relapse, or had refractory disease or persistent positive minimal residual disease (MRD) at the end of consolidation. Methods: This is a retrospective, observational cohort study enrolled in 11 consecutive patients with AML or MDS with excess blasts (MDS-EB). Venetoclax was given at a dose of 400 mg/day for 28 days per cycle. Decitabine was given at a dose of 20 mg/m2/day for 5 days (n=3) or azacytidine (n=8) was given at a dose of 75 mg/m2/day for 7 days at the discretion of the treating physician. Cytarabine was given at a dose of 10 mg/m2 twice daily for 7 days. This study was approved by the Ethics Committee of the Chinese PLA General Hospital, and signed informed consents were obtained from all patients prior to treatment in accordance with principles of Declaration of Helsinki. Results: As shown in Figure 1, overall response rate was 72.7%. Three of the 6 patients with relapsed and refractory diseases achieved MRD-negative complete remission. Remarkably, all of the 5 patients with persistence or relapse of MRD achieved durable MRD-negative remission. Majority of patients (10/11) were heavily pretreated with an Eastern Cooperative Oncology Group score of 2-3, whereas no early mortality (death within 90 days of therapy initiation) was recorded and disease relapse was the only cause of death. The estimated 1-year overall survival and relapse-free survival rates were 72.9% (95%CI, 27.6%-92.5%) and 58.3% (95%CI, 7.7%-89.3%), respectively. Image:Summary/Conclusion: This study highlights the promising activity and safety of the venetoclax-based triple-drug regimen in patients with relapsed/refractory AML or MDS unfit for intensive chemotherapy and patients with persistent MRD.
PB1765: EFFICACY OF A NEW INDUCTION REGIMEN IN THE TREATMENT OF EARLY T-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA.
Authors: M. Wang, J. Rao, Q. Wen, G. Chen, X. Tan, Y. Ma, L. Gao, L. Gao, P. Kong, C. Zhang, X. Zhang
Journal: HemaSphere (2022)

Background: There is no standard induction chenotherapy for adult acute lymphoblastic leukemia. Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) has poor response to standard intensive chemotherapy, high risk of recurrence and poor prognosis. Aims: To explore the appropriate induction program to improve the remission rate and prolong the survival period. Methods: A total of 21 newly diagnosed patients with ETP-ALL who received induction chemotherapy with different regimens in the Second Affiliated Hospital of Chongqing Army Military Medical University (Xinqiao Hospital) from January 2017 to December 2020 were retrospectively analyzed for efficacy and main adverse reactions.The initial diagnosis of ETP-ALL was based on the results of bone marrow cytology and flow cytometry immunophenotype. Results: The 21 patients included 14 males and 7 females, with a median age of 27(16-57) years. Among them, 7 patients received PCIOD program and 14 patients received VTLP like program.Among the 7 patients who received PCIOD, 5 patients achieved cytological response (71.43%), and 2 patients were MRD negative (28.57%).In VTLP-like regimen, 7 patients (50%) had cytological remission, of which 1 patient (7.14%) was MRD negative.Major adverse reactions: bone marrow suppression, granulocytopia with fever and septicemia were the major adverse reactions after chemotherapy.Among the 7 patients with PCIOD, 3 patients developed pulmonary infection, including 1 patient with sepsis (klebsiella pneumoniae), while 5 patients with VTLP-like regimen developed pulmonary infection, 3 patients with sepsis, and 2 patients with acute pancreatitis.It did not increase the incidence of major adverse events compared with conventional regimens.There was no treatment-related mortality in any of the patients. Summary/Conclusion: ETP-ALL induced remission rate is low, malignant degree is high, prone to early recurrence and short survival.PCIOD regimen can improve the complete response rate and MRD conversion rate of ETP-ALL patients, and does not increase the treatment-related mortality. However, due to the small number of cases, it needs to be further confirmed by multi-center, randomized controlled studies.
Abstract SY39-01: The DNA damageome and cancer evolution
Authors: Susan Rosenberg
Journal: Cancer Research (2022)

Abstract DNA damage provokes mutations, genome instability, cancer and biological aging and results from external agents or endogenous cellular processes. We identified networks of unrelated proteins of diverse functions that promote DNA damage when overproduced: the DNA “damageome” proteins (DDPs). We found a large overproduction DDP network in Escherichia coli and find that the proteins promote mutagenesis and genome instability by various mechanisms—three of which we identify. Their 284 human homologs are over-represented among known cancer drivers, and their expression in tumors predicts heavy mutagenesis and poor prognosis. When overproduced in human cells, many of the human homologs promote DNA damage and mutation, with DNA-damaging mechanisms like those in E. coli. As the earliest upstream provocateurs of cancer evolution, the proteins of DNA damageome networks may indicate that there are evolution-accelerating functions of many human known and newly implicated cancer-promoting proteins. Citation Format: Susan Rosenberg. The DNA damageome and cancer evolution [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr SY39-01.
PB2046: SHORT-TERM EFFICACY OF DECITABINE IN COMBINATION WITH LOW-DOSE CHEMOTHERAPY IN THE TREATMENT OF JMML: A RETROSPECTIVE STUDY
Authors: Y. Cai, J. Zhang, M. Yi, W. Zhang, X. Liu, X. Zhang, Y. Wan, L. Chang, L. Zhang, X. Chen, Y. Guo, Y. Zou, Y. Chen, J. Li, Y. Zhang, W. Yang, X. Zhu
Journal: HemaSphere (2022)

Background: Juvenile myelomonocytic leukemia (JMML) is an aggressive pediatric myeloproliferative disease, but several newly diagnosed patients cannot tolerate hematopoietic stem cell transplantation (HSCT) at diagnosis. Aims: n the present study, we aimed to explore the short-term effect of decitabine in combination with low-dose chemotherapy on improving the condition of JMML patients before HSCT. Methods: A total of 10 JMML patients were enrolled in this retrospective analysis. All the patients were treated with decitabine supplemented with low-dose chemotherapy with a interval of 4 weeks, bridging to HSCT after three~four courses. Results: The median treatment course was three (one-five) cycles, and the response rate was 70.0% after one cycle and 71.4% after three cycles. The WBC and monocyte counts were significantly decreased after chemotherapy, and the spleen volume showed a decreasing tendency. The 12-month progression-free survival rate was 80.0±12.6%. Image:Summary/Conclusion: Decitabine in combination with low-dose chemotherapy was favorable in reducing tumor burden and improving the clinical status.
PB1965: A META-ANALYSIS OF THE RATE OF MALIGNANT PROGRESSION OF MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE: PRELIMINARY FINDINGS FROM A SYSTEMATIC REVIEW
Authors: S. J. Quinn, C. Cardwell, L. Anderson, C. McShane
Journal: HemaSphere (2022)

Background: Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant condition preceding multiple myeloma (MM) and other haematological malignancies (HM). Clinically the rate of progression from MGUS to HM is important; current guidelines from the International Myeloma Working Group (IMWG) report this rate as “around 1% per year”, however variation has been reported by ethnic groups, MGUS type, and clinical features. Aims: A systematic review of the published literature was conducted to investigate the rate of MGUS progression to support clinical practice. Methods: Four electronic databases (Embase, Medline, Pubmed and Web of Science) were searched from database inception to 11/12/2019 using key words and MeSH subject headings for “MGUS”, “haematological malignancy” and “progression”. Studies were reviewed against predefined eligibility criteria by two independent reviewers. For studies reporting progression events and person-years of follow-up, a random-effects meta-analysis model5 was used to produce a pooled rate of MGUS progression to HM and MM. Studies reporting on cumulative rates of progression at specified time-points (1, 5 and 10-year) were included in a narrative synthesis. Results: Overall, 36 papers met the inclusion criteria; 12 studies (sample size: 114-17,963; follow-up 3.3-42.1 years) were included in the meta-analysis. In preliminary analyses, the annual pooled rate of MGUS progression was 1.1% (95%CI 0.9-1.3) to HM and 0.9% (95%CI 0.7-1.1) to MM. In total, 18 studies contributed to the narrative synthesis on MGUS progression to HM (sample size: 52-17,963; follow-up 2.1-34.1 years) and 10 studies reported on MGUS progression to MM (sample size: 75-2046, follow-up: 2.1-17 years). These narrative syntheses highlighted the heterogeneity of research, which encompassed key traits like methods, sample sizes and follow-up duration. Studies were also mainly conducted in Europe, being particularly scarce in Asia. Between meta-analysis and narrative synthesis, only seven studies reported on IgM-MGUS progression to Waldenström’s macroglobinaemia or HM, which could not be clearly synthesised in either analysis due to differing reporting; these papers indicated higher progression rates in IgM-MGUS than non-IgM. Summary/Conclusion: Preliminary findings from this systematic review support current IMWG guidelines on the rate of MGUS progression to HM. However, as the majority of studies included were limited to geographic areas within Europe and USA, further research reflecting population and clinical diversity are needed.